FDA Warning Letter: Visible Particles and Visual Inspection

During an FDA inspection at the Kansas-based company Hospira in mid 2016, the authority encountered several GMP violations which resulted in a Warning Letter.

The GMP deficiencies concerning visual inspection as well as the handling of distributed batches which were contaminated with particles even lead to the assertion that the company's process of manufacturing injectable products was out of control. During the inspection, the FDA found numerous internal investigations concerning particulate matter in batches of parenteral products. In regards to visible particles in sterile lots of injectables, the FDA speaks of a "significant loss of control in the manufacturing process".

A complaint was made for a batch because of visible particles, for example. This was confirmed; there were pieces of cardboard found in the respective retain samples. They were put down to the handling of vial stoppers, however the investigation was closed without a proper evaluation or corrective measures being taken. Even when another batch containing the same kind of particles was complained about at a later date, no further actions were instigated.

The batch the cardboard particles had originally been found in hadn't been called back until four months after the complaint. An investigation confirmed this, 190 retain samples of the batch were also found contaminated. A subsequent investigation was found insufficient by the FDA. In their report, the FDA criticises the lacking scientific rationale for the chosen number of vials to be tested, as well as the missing description of the examination method.

The batch was distributed even though the found particulate matter had been detected in other batches before. It was claimed that the presence of particles was "intrinsic to the manufacturing process". The FDA further criticises the lack of a specific identification of the particles in question, that there was no investigation into other potentially affected batches and the missing corrective actions.

The visual inspection, semi- as well as fully-automatic, was also objected to by the FDA; there were no warning and action limits. The procedures for visual inspection instruct operators to ignore defect limits following changes to the inspection process.

Source: FDA Warning Letter to Hospira Inc. from February 14, 2017